Physiological sensor delivery device and method

ABSTRACT

Sensor delivery devices and methods of measuring Fractional Flow Reserve in a patient are disclosed. One sensor delivery device includes a distal sleeve, a proximal portion, and a pressure sensor. The distal sleeve is configured to be advanced through a patient&#39;s vasculature over a guidewire. The pressure sensor is located on the distal sleeve or the proximal portion. The pressure sensor is adapted to generate a signal proportional to fluid pressure. The pressure sensor includes a material having a low thermal coefficient of pressure.

RELATED APPLICATION

This application is a divisional of, and claims priority to, U.S. patentapplication Ser. No. 14/300,654, filed Jun. 10, 2014, the entirecontents of which are hereby incorporated by reference.

TECHNICAL FIELD

This application relates generally to the field of medical devicetechnology and, more particularly, to devices and methods forpositioning and utilizing physiological sensors in anatomical (e.g.,vascular) structures of patients, such as in blood vessels or acrossheart valves.

BACKGROUND

Certain physiological measurements may be made by positioning a sensorwithin a patient. Such physiological measurements may include, forexample, measurements of blood parameters, such as blood pressure,oxygen saturation levels, blood pH, etc. Some such measurements may havediagnostic value and/or may form the basis for therapy decisions.

A technique for evaluating the degree to which a stenotic lesionobstructs flow through a blood vessel is called the Fractional FlowReserve measurement (FFR). To calculate the FFR for a given stenosis,two blood pressure readings are taken. One pressure reading is taken onthe distal side of the stenosis (e.g., downstream from the stenosis),the other pressure reading is taken on the proximal side of the stenosis(e.g., upstream from the stenosis, towards the aorta). The FFR isdefined as the ratio of maximal blood flow in a stenotic artery, takendistal to the lesion, to normal maximal flow, and is typicallycalculated based on a measured pressure gradient of the distal pressureto the proximal pressure. The FFR is therefore a unitless ratio of thedistal and proximal pressures. The pressure gradient, or pressure drop,across a stenotic lesion is an indicator of the severity of thestenosis, and the FFR is a useful tool in assessing the pressure drop.The more restrictive the stenosis is, the greater the pressure drop, andthe lower the resulting FFR. The FFR measurement may be a usefuldiagnostic tool. For example, clinical studies have shown that an FFR ofless than about 0.75 may be a useful criterion on which to base certaintherapy decisions. Pijls, DeBruyne et al., Measurement of FractionalFlow Reserve to Assess the Functional Severity of Coronary ArteryStenoses, 334:1703-1708, New England Journal of Medicine, Jun. 27, 1996.A physician might decide, for example, to perform an interventionalprocedure (e.g., angioplasty or stent placement) when the FFR for agiven stenotic lesion is below 0.75, and may decide to forego suchtreatment for lesions where the FFR is above 0.75. Thus, the FFRmeasurement could become a decision point for guiding treatmentdecisions.

One method of measuring the pressure gradient across a lesion is to usea small catheter connected to a blood pressure measurement sensor. Thecatheter would be passed over the guidewire which has already beenplaced across the lesion. The catheter would be advanced down theguidewire until the tip of the catheter crosses the lesion. The bloodpressure on the distal side of the lesion is recorded. This pressurewould be divided by the pressure value recorded in the aorta. Adisadvantage of using this method is that some error may be introduceddue to the cross sectional size of the catheter. As the catheter crossesthe lesion, the catheter itself introduces blockage, in addition to thatcaused by the lesion itself. The measured distal pressure wouldtherefore be somewhat lower than it would be without the additional flowobstruction, which may exaggerate the measured pressure gradient acrossthe lesion.

Pressure drop can also be measured across a heart valve. When a heartvalve is regurgitant, a less than optimal pressure drop is typicallyobserved. Using a catheter to measure pressure drop is common across aheart valve. However, because of the catheter size, the heart valve maynot seal well around the catheter. Leakage might also result from thepresence of the catheter and may contribute to an inaccurate pressuredrop reading. One example of where this could occur is in the mitralvalve (e.g., mitral valve regurgitation).

One method of measuring blood pressure in a patient is to use a pressuresensing guidewire. Such a device has a pressure sensor embedded withinthe guidewire itself. A pressure sensing guidewire could be used in thedeployment of interventional devices such as angioplasty balloons orstents. Prior to the intervention, the pressure sensing guidewire wouldbe deployed across a stenotic lesion so the sensing element is on thedistal side of the lesion and the distal blood pressure is recorded. Theguidewire may then be retracted so the sensing element is on theproximal side of the lesion. The pressure gradient across the stenosisand the resulting FFR value could then be calculated.

To use a guidewire-based pressure sensor in certain applications, theguidewire must be repositioned so the sensing element of the guidewireis correctly placed with respect to a stenotic lesion, for example.Blood pressure measurements for calculating FFR, for example, aregenerally taken on both sides of a given stenosis, so the guidewire istypically retracted across the stenosis to make the upstreammeasurement. After retracting the guidewire to make the proximalpressure measurement (aortic pressure or upstream coronary pressure),the guidewire may again be repositioned downstream of the lesion, forexample, if it is determined (e.g., based on the FFR calculation) thatan interventional device should be deployed. In cases where there aremultiple lesions, the sensing element of a pressure sensing guidewirewould need to be advanced and retracted across multiple lesions, andwould potentially have to be advanced and repositioned again for eachsuch lesion. Advancing and maneuvering a pressure sensing guidewirethough stenotic lesions and the vasculature, for example, can be adifficult and/or time consuming task.

Physician preference is another factor that may influence the choice ofdiagnostic tools or techniques used for certain applications. Forexample, some physicians may tend to become accustomed to using certainspecific guidewires for certain applications. “Standard” (e.g.,commercially available) medical guidewires may vary in size,flexibility, and torque characteristics. A physician may prefer to usedifferent guidewires for different tasks, for example, to accesshard-to-reach anatomical areas, or when encountering bifurcations inarteries. Certain guidewires may therefore be better suited for specifictasks because of the torque and flexing characteristics, and a physicianmay display a strong preference for using a certain guidewire based onthe specific task (or tasks) he or she is facing. A pressure sensingguidewire may have torque and flexing characteristics that are eitherunknown to the physician, or that are unsuitable for a particular task,because such a guidewire is specifically constructed to have a pressuresensor incorporated as part of the guidewire itself. As a result, aphysician may find it difficult to maneuver a pressure sensing guidewireinto an anatomical location of interest, as compared to a “standard”(e.g., non-pressure sensing) medical guidewire.

Having grown accustomed to the handling characteristics of a particularnon-pressure sensing guidewire, a physician may be reluctant to employ apressure sensing guidewire, which may increase the time and difficultyof positioning and repositioning the pressure sensing guidewire across astenotic lesion, for example. In such cases, a physician may choose toforego the benefit of a diagnostic measurement, such as FFR, and simplychoose to deploy some form of interventional therapy as a conservativeapproach to such decisions. If the diagnostic measurement techniques andthe associated devices were simple enough to use, more physicians woulduse them and thereby make better therapy decisions.

SUMMARY

Physiological sensor delivery devices and methods according toembodiments of the invention may be used in diagnostic applications,such as cardiovascular procedures in coronary arteries, interventionalradiology applications in peripheral arteries, and structural heartapplications in heart valves.

In some embodiments, the methods include measuring FFR in a patientusing a sensor delivery device. The sensor deliver device may include adistal sleeve, a distal sensor located on the distal sleeve, a proximalsensor located on the distal sleeve and proximal to the distal sensor, aproximal portion, and a communication channel, the sensors adapted togenerate signals proportional to fluid pressure. The method may includeadvancing a guidewire through a patient's vasculature to a location ofinterest in a patient, advancing a guiding catheter over the guidewireto the location of interest, advancing a sensor delivery device withinthe guiding catheter to the location of interest, advancing only adistal portion of the distal sleeve outside of the guiding catheter suchthat the distal sensor is outside of the guiding catheter and downstreamof the location of interest and the proximal sensor is inside of theguiding catheter, measuring a distal fluid pressure with the distalsensor distal to the location of interest, measuring a reference fluidpressure with the proximal sensor inside of the guiding catheter, andcalculating FFR using the measured distal fluid pressure and thereference fluid pressure. The FFR may be calculated as a ratio of thesensor signal to the fluid pressure signal. The method may furtherinclude making a therapy decision based on the calculated FFR beingbelow a threshold value. For example, the therapy decision may beselecting an interventional therapy if the calculated FFR is less thanabout 0.75. In some embodiments, the method further includes withdrawingthe device and deploying an interventional therapy device using the sameguidewire used to position the sensor downstream of the location ofinterest.

In some embodiments, the steps of measuring a distal fluid pressure withthe distal sensor distal to the location of interest and of measuring areference fluid pressure with the proximal sensor inside of the guidingcatheter are performed after the step of advancing only a distal portionof the distal sleeve, without advancing or retracting the distal sleeve.In some embodiments, the method also includes normalizing the sensorsignal to the fluid pressure signal prior to positioning the sensordownstream of the location of interest.

In some embodiments, one or both of the proximal and sensors has a lowthermal coefficient. In some embodiments, only one of the proximal anddistal sensors has a low thermal coefficient, and the method includes,before advancing the sensor delivery device to the location of interest,calibrating the sensor having a low thermal coefficient to atmosphericpressure, and after advancing the sensor delivery device to the locationof interest and before measuring a distal fluid pressure or a referencefluid pressure, calibrating the sensor which is does not have a lowthermal coefficient to be equal to the sensor having a low thermalcoefficient.

In other embodiments, the method includes calibrating a low thermalcoefficient sensor of a sensor delivery device to atmospheric pressurewhile located outside of the patient, wherein the sensor delivery devicecomprises the low thermal coefficient sensor and a non-low thermalcoefficient sensor, advancing the sensor delivery device to a locationof interest within the patient's body, equilibrating the non-low thermalcoefficient sensor to the low thermal coefficient sensor, afterequilibrating the sensors, positioning one of the sensors distal to thelocation of interest and measuring a distal pressure and measuring aproximal pressure with the other of the sensors, and calculating FFRusing the measured distal fluid pressure and the reference fluidpressure. The method may further include measuring the proximal pressurewhile the sensor is located within a guiding catheter.

In some embodiments, the device includes a sensor delivery deviceincluding a distal sleeve configured to be advanced through a patient'svasculature over a guidewire, the distal sleeve including a distalsensor located on the distal sleeve, a proximal sensor located on thedistal sleeve and proximal to the distal sensor, a proximal portion, anda communication channel, the sensors adapted to generate signalsproportional to fluid pressure. One or both of the distal sensor and theproximal sensor may be comprised of a material having a low thermalcoefficient. For example, the thermal coefficient of the material may beless than or equal to approximately 0.1 mmHg/° C. The thermalcoefficient of the material of the sensor allows the sensor to becalibrated to atmospheric pressure outside of a patient's body atapproximately room temperature and to remain calibrated to atmosphericpressure after insertion into a patient's body. In some embodiments,both the proximal and distal sensors are comprised of material having alow thermal coefficient. The device may further include a guidewireand/or a guiding catheter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a sensor delivery device according to anembodiment of the invention;

FIG. 2 is a conceptual perspective view of a sensor delivery device formaking physiological measurements according to an embodiment of theinvention;

FIG. 3 is an conceptual plot of a patient's blood pressure as a functionof time;

FIG. 4(a) is a side view of a sensor delivery device according to anembodiment of the invention having one or more flow holes disposed alonga side portion;

FIG. 4(b) is a cross-sectional view of a sensor delivery deviceaccording to an embodiment having one or more flow holes;

FIG. 5(a) is a cut-away side view of a sensor delivery device with asensor housing according to one embodiment of the invention;

FIG. 5(b) is a cut-away side view of a sensor delivery device with asensor housing according to one embodiment of the invention;

FIGS. 5(c) and 5(d) are side views of a sensor delivery device withradiopaque marker band according to certain embodiments of theinvention;

FIG. 5(e) is a cut-away side view of a sensor delivery device with astrain relief spacer according to one embodiment of the invention;

FIGS. 6(a)-6(g) are enlarged side views of a distal transition of asensor delivery device according to certain embodiments of theinvention;

FIGS. 7(a) and 7(b) are perspective views of a sensor delivery devicehaving a second sensor disposed on a proximal sleeve according to anembodiment of the invention;

FIG. 8 is a perspective view of a sensor delivery device having afurcation tube according to an embodiment of the invention;

FIG. 9 is a cross-sectional side view of a sensor delivery device havinga dual lumen configuration according to one embodiment of the invention;

FIG. 10(a)-(c) is a side view of a sensor delivery device having anover-the-wire configuration according to one embodiment of theinvention;

FIG. 11 is a flow diagram showing a method of using a sensor deliverydevice according to certain embodiments of the invention;

FIG. 12 is a perspective view of a fluid injection system that may beused to interact with a sensor delivery device according to anembodiment of the invention;

FIG. 13 is a perspective view of a fluid injection system that may beused to interact with a sensor delivery device according to anembodiment of the invention;

FIG. 14 is a flow diagram of a method of using a sensor delivery devicein conjunction with a fluid injection system according to certainembodiments of the invention;

FIG. 15 is a flow diagram of a method of using a sensor delivery deviceaccording to an embodiment of the invention;

FIG. 16 is a perspective view of a powered injection system adapted tobe coupled to a physiological sensor delivery device according tocertain embodiments of the invention; and

FIG. 17 is an idealized view of a user interface screen containinginformation that may be displayed to an operator, according to certainembodiments of the invention.

DETAILED DESCRIPTION

The following detailed description should be read with reference to theaccompanying drawings, in which like numerals denote like elements. Thedrawings, which are not necessarily to scale, depict selectedembodiments of the invention—other possible embodiments may becomereadily apparent to those of ordinary skill in the art with the benefitof these teachings. Thus, the embodiments shown in the accompanyingdrawings and described below are provided for illustrative purposes, andare not intended to limit the scope of the invention as defined in theclaims appended hereto.

An example of a sensor delivery device according to certain embodimentsof the invention is shown in FIG. 1. The sensor delivery device 10 ofFIG. 1 includes a distal sleeve 20 having a guidewire lumen 22 forslidably receiving a medical guidewire 30. A sensor 40 is coupled to thedistal sleeve 20, sensor 40 being capable of sensing and/or measuring aphysiological parameter of a patient and generating a signalrepresentative of the physiological parameter. Thus, the distal sleeve20, and hence, the sensor 40, may be positioned within a patient (e.g.,within an anatomical structure of a patient, such as within a vein,artery, or other blood vessel, or across a heart valve, for example) bycausing the distal sleeve 20 to slide over the medical guidewire 30 tothe desired position.

The sensor delivery device 10 of FIG. 1 also includes a proximal portion50, which is coupled to the distal sleeve 20. The proximal portion 50includes a communication channel 60 for communicating the signal fromthe sensor 40 to a location outside of the patient (e.g., to aprocessor, display, computer, monitor, or to another medical device).Communication channel 60 may comprise a fiber optic communicationchannel in certain preferred embodiments, such as where the sensor 40 isa fiber optic pressure sensor. Alternately, communication channel 60 maycomprise an electrically conductive medium, such as one or moreelectrical conducting wires. Of course, many other forms ofcommunication media may be suitable for transmitting the signalgenerated by sensor 40 to a location outside of the patient. In someembodiments of the invention, the communication channel 60 may compriseany of a variety of fluid and/or non-fluid communication media, such asa wireless communication link, or an infrared capability, or acousticcommunications such as ultrasound, as possible examples.

The proximal portion 50 is also adapted to assist an operator (e.g., aphysician or other medical staff) in positioning the distal sleeve 20and the sensor 40 within an anatomical (e.g., vascular) structure of thepatient. This is typically accomplished by an operator first inserting a“standard” medical guidewire 30 into a patient's vasculature andadvancing it past an area of interest. The sensor delivery device 10 isthen deployed by “threading” the distal sleeve 20 onto the guidewire 30such that the lumen 22 slides over the guidewire 30, and advancing thedistal sleeve 20 (and the associated sensor 40) by moving (e.g., pushingand/or pulling) the proximal portion 50 until sensor 40 is in thedesired location.

The device 10 and the guidewire 30 are typically manipulated inside aguiding catheter 32, which has been placed in the anatomical (e.g.,vascular) structure of interest. In certain preferred embodiments of theinvention, the guidewire lumen 22 may be sized to slide over “standard”sized medical guidewires. For example, a number of manufacturers makemedical guidewires that range in size from less than about 0.014 inchesouter diameter to more than about 0.038 inches outer diameter, typicallyhaving a finite number of common sizes within this range. “Standard”size medical guidewires might, for example, have outer diameters of0.010, 0.014, 0.018, 0.021, 0.025, 0.028, 0.032, 0.035, and 0.038inches. Thus, in certain preferred embodiments of the invention, theguidewire lumen 22 may be sized appropriately to slide over a particularstandard size medical guidewire. A device according to preferredembodiments of the invention may therefore be made available in a rangeof sizes corresponding to standard medical guidewire sizes.

One potential advantage of a sensor delivery device 10 according toembodiments of the invention is that it allows a physician to use theguidewire of their choice. Sensor delivery device 10 can be sized to beused with any guidewire. The physician may, for example, choose aparticular guidewire based on its unique flexing and torquecharacteristics for certain procedures. Delivery device 10 according tovarious embodiments of the invention provides the physician with theability to use whichever guidewire is deemed best suited for theparticular application.

Another potential advantage of the sensor delivery device 10 is that itdoes not require repositioning of the guidewire in order to make sensorreadings. Once the guidewire has been positioned across a stenoticlesion, for example, the sensor delivery device 10 can be positioned(e.g., advanced and/or retracted) over the guidewire and the sensor 40can therefore be advanced and retracted across lesions to make pressurereadings, for example, without moving the guidewire. A physician mayalso save time by not having to reposition the guidewire across thelesion or lesions to make such measurements.

In the example shown in FIG. 1, the device 10 is being deployed usingguiding catheter 32, which has been placed within a vascular structureof interest (in this example, blood vessel 34, which could be, forexample, a coronary artery of the patient). In certain embodiments ofthe invention, the size or “footprint” (e.g., the width and/or thecross-sectional area) of device 10 may allow it to fit within certainstandard sized guiding catheters. For example, in certain diagnosticapplications, it would be desirable to have device 10 deployed within acertain sized guiding catheter (e.g., smaller than about 4 or 5 French(FR)).

In certain embodiments of the invention, the distal sleeve 20 of thedevice may be substantially concentric with the guidewire 30. Thecoupling of the proximal portion 50 to the distal sleeve 20 allows theguidewire 30 to separate from the rest of device 10 (e.g., in what issometimes referred to as a “monorail” catheter configuration); thiswould typically occur inside the guiding catheter 32. The guidewire 30and device 10 would both exit the patient at the proximal end of theguiding catheter 32 as separate devices. Having the device 10 andguidewire 30 separate allows the physician to independently controldevice 10 and guidewire 30, as necessary. It may also allow a physicianto use a shorter guidewire for catheter exchange. For example, amonorail-type configuration may allow for the use of a guidewire that isapproximately 170 to 200 cm long, whereas an “over-the-wire”configuration might require the use of a much longer (e.g., up to 300 cmor more) guidewire. Having the device 10 and guidewire 30 separate(except at the distal sleeve 20) may also result in less friction (e.g.,within the guiding catheter 32) than if the device 10 and guidewire 30had to be moved together as a unit. In some embodiments, a hydrophiliccoating may be applied to various portions of the device to furtherreduce the amount of friction encountered, for example, when advancingor retracting device 10.

One diagnostic application in which various embodiments of the inventionmay be well-suited is the measurement of Fractional Flow Reserve (FFR).As noted above, the FFR measurement quantifies the degree to which astenotic lesion, for example, obstructs flow through a blood vessel. Tocalculate the FFR for a given stenosis, two blood pressure measurementsare needed: one pressure reading is taken on the distal side of thestenosis (downstream side), the other pressure reading is taken on theproximal side of the stenosis (upstream side). The FFR is therefore aunitless ratio of the distal pressure to the proximal pressure. Thepressure gradient across a stenotic lesion is an indicator of theseverity of the stenosis. The more restrictive the stenosis is, the morethe pressure drop, and the lower the FFR.

To add clarity and context to the disclosure, several embodiments of theinvention will now be described below in the context of making FFRmeasurements. However, it should be realized that there are otherapplications in which physiological parameter measurements could befacilitated with the devices and/or methods described herein.

FIG. 2 is a perspective view of a sensor delivery device for measuring aphysiological parameter in a patient according to an embodiment of theinvention. The embodiment shown in FIG. 2 might, for example, bedeployed to make an FFR measurement in a blood vessel of a patient. FIG.2 shows a sensor delivery device 210 being deployed in a blood vessel ofa patient (e.g., coronary artery 234) across a stenosis (e.g., stenoticlesion 236). To make an FFR measurement, for example, first sensor 240may be positioned to measure distal (downstream) blood pressure, P_(d),at a location 231 downstream of a location of interest (e.g., stenoticlesion 236). First sensor 240 may then be positioned to measure proximal(upstream) blood pressure, P_(p), at a location 233 upstream of alocation of interest (e.g., stenotic lesion 236). FFR is simplycalculated as the ratio of distal pressure to proximal pressure, orFFR=(P_(d)/P_(p)). The use of the terms “downstream” and “upstream” arewith respect to the normal direction of blood flow, “D,” as shown inFIG. 2.

In FIG. 2, first sensor 240 is coupled to distal sleeve 220. In theembodiment shown in FIG. 2, first sensor 240 is coupled to an outersurface of distal sleeve 220. The first sensor 240 is adapted to measurea physiological parameter of a patient, such as a blood parameter (e.g.,blood pressure, temperature, pH, blood oxygen saturation levels, etc.),and generate a signal representative of the physiological parameter. Incertain preferred embodiments of the invention, the first sensor 240 isa fiber optic pressure sensor adapted to measure blood pressure. Anexample of a fiber optic pressure sensor is a Fabry-Perot fiber opticpressure sensor, which is a commercially available sensor. Examples ofFabry-Perot fiber optic sensors are the “OPP-M” MEMS-based fiber opticpressure sensor (400 micron size) manufactured by Opsens (Quebec,Canada), and the “FOP-MIME” sensor (515 micron size) manufactured byFiso Technologies, Inc. (Quebec, Canada). In certain alternateembodiments, first sensor 240 may be a piezo-resistive pressure sensor(e.g., a MEMS piezo-resistive pressure sensor), and in otherembodiments, first sensor 240 may be a capacitive pressure sensor (e.g.,a MEMS capacitive pressure sensor). A pressure sensing range from about−50 mm Hg to about +300 mm Hg (relative to atmospheric pressure) isdesired for making most physiological measurements with sensor 240, forexample.

In embodiments of the invention using the Fabry-Perot fiber opticpressure sensor as the sensor 240, such a sensor works by having areflective diaphragm that varies a cavity length measurement accordingto the pressure against the diaphragm. Coherent light from a lightsource travels down the fiber and crosses a small cavity at the sensorend. The reflective diaphragm reflects a portion of the light signalback into the fiber. The reflected light travels back through the fiberto a detector at the light source end of the fiber. The two light waves,the source light and reflected light travel in opposite directions andinterfere with each other. The amount of interference will varydepending on the cavity length. The cavity length will change as thediaphragm deflects under pressure. The amount of interference isregistered by a fringe pattern detector.

FIG. 2 shows proximal portion 250 coupled to the distal sleeve 220. Theproximal portion 250 includes a communication channel 260 forcommunicating the physiological signal from the sensor 240 to a locationoutside of the patient (e.g., to a processor, display, computer,monitor, or to another medical device). The proximal portion 250 maypreferably be formed of a material of sufficient stiffness in order toassist an operator (e.g., a physician or other medical staff) inpositioning the distal sleeve 220 and the sensor 240 within ananatomical (e.g., vascular) structure of the patient.

One suitable material for the proximal portion 250 may be a stainlesssteel hypotube, for example. Depending on the application, the proximalportion 250 (sometimes also referred to as the “delivery tube”) shouldtypically be stiffer and more rigid than the distal sleeve 220 in orderto provide a reasonable amount of control to push, pull and otherwisemaneuver the device to a physiological location of interest within thepatient. In interventional cardiology procedures, for example, at leasta portion of the proximal portion 250 will be maneuvered within aguiding catheter positioned within the aortic artery. The proximalportion 250 in such an application should therefore be flexible enoughto accommodate the arch of the aorta, while being rigid enough to pushand pull the device. Accordingly, suitable materials for proximalportion 250 may also include (in addition to the aforementionedstainless steel hypotube) materials such as nitinol, nylon, and plastic,for example, or composites of multiple materials.

The communication channel 260 may be disposed along an outer surface ofproximal portion 250, or may be formed within the proximal portion 250,as shown in FIG. 2. For example, communication channel 260 may comprisea communication lumen that extends longitudinally through proximalportion 250 in some embodiments. Communication channel 260 may comprisea fiber optic communication channel in certain embodiments, such aswhere the sensor 240 is a fiber optic pressure sensor. Alternately,communication channel 260 may comprise an electrically conductivemedium, such as electrical conducting wires, or other communicationmedia suitable for transmitting the signal generated by sensor 240. Inpreferred embodiments of the invention, the communication channel 260comprises a non-fluid communication medium. In the embodiment shown inFIG. 2, communication channel 260 (e.g., a fiber optic cable) extendsdistally beyond proximal portion 250 and is coupled to sensor 240. Thecommunication channel 260 in such an embodiment is at least partiallyhoused within a communication lumen of the proximal portion 250 (e.g., astainless steel hypotube).

FIG. 2 also shows an optional embodiment of the invention in which asecond sensor 242 may be coupled to the device 210. For example, asecond sensor 242 may be coupled to proximal portion 250 such that thefirst and second sensor 240, 242 are spaced apart sufficiently (e.g., afixed distance apart) to span a stenotic lesion. This embodiment mayoffer the ability to measure FFR without having to reposition device210, since first sensor 240 could be placed distal of the stenoticlesion 236 to measure P_(d), and second sensor 242 could be placedproximal of the stenotic lesion 236 to measure P_(p). Second sensor 242may have a communication channel 262, which could be housed withinproximal portion 250, or could be disposed along an outside surface ofproximal portion 250, as shown in FIG. 2, for example. Further, theability to measure P_(d) and P_(p) substantially simultaneously mayimprove accuracy and/or reduce the effects of certain types of errorsillustrated and described below with reference to FIG. 3.

It should be noted that certain embodiments could have more than 2sensors, and that the spacing between adjacent sensors in suchembodiments may be varied to provide a variable spacing capability. Incertain alternate embodiments of the invention, one or more sensorscould be disposed on the proximal portion 250 with no sensors disposedon the distal sleeve 220, for example. In some alternate embodiments, itmay be desirable to have a plurality of sensors (two, or three, or four,or more sensors) spaced at known, fixed distances, disposed along theproximal portion 250. This could, for example, provide the ability tomeasure P_(d) and P_(p) substantially simultaneously, regardless oflesion length, by selecting an appropriate pair of sensors (from amongthe plurality of sensors) placed across the lesion from which to obtainthe P_(d) and P_(p) signals. Further, the sensors could have some formof radiopaque markings incorporated thereon (e.g., marker bands), whichcould provide a visual estimate of lesion size in conjunction with themeasurement of physiological parameters (e.g., P_(d) and P_(p)).

In some embodiments, it may be desirable to measure the distal pressureP_(d) with the sensor outside of (extended distal to the distal end of)the guiding catheter, while the proximal pressure P_(p) is measured bysensor 240 or 242 within the guiding catheter. In this way, it can beassured that the proximal measurement is taken proximal to the lesionand not mistakenly taken within the lesion. If the proximal pressureP_(p) measurement were obtained within the location of interest such asa lesion, the measurement could be inaccurate, resulting in an erroneousFFR and potentially inaccurate treatment recommendations. Embodiments inwhich the P_(p) is taken within the guiding catheter therefore minimizeor prevent this type of error, improving the accuracy of FFRcalculations and subsequent treatment decisions.

In embodiments having only a single sensor 240, this may be achieved byeither first measuring P_(p) within the guiding catheter, and thenextending the distal sleeve to position the sensor 240 downstream of thelocation of interest to measure P_(d). Alternatively, the distal sleevemay be extended to position the sensor 240 downstream of the location ofinterest to measure P_(d) and may then be retracted across the locationof interest and into the guiding catheter to measure P_(p). Inembodiments having two or more sensors, the first sensor 240 may bepositioned downstream of the location of interest to measure P_(d) whilethe second sensor 242 or other more proximal sensor is positionedproximal to the location of interest and within the guiding catheter tomeasure P_(p). The device 210 may be configured such that the length ofthe guiding catheter and the distance between the first sensor 240 andthe second sensor 242 or other more proximal sensor are adequate toallow the distal sensor to be located distal to the location of interestwhile the proximal sensor remains proximal and within the guidingcatheter without adjusting position, with the location of interest at avarying distance from the distal end of the guiding catheter. Forexample, location of interest may be located between about 10 and about30 centimeters distal to the distal end of the guiding catheter. Thedevice 210 may be configured such that the spacing between the firstsensor 240 and the second sensor 242 or other sensor, and the length ofthe guiding catheter within which the second sensor 242 or other sensormeasures P_(p), is adequate to allow the first sensor 240 to bepositioned distal to the location of interest to measure P_(d), with theproximal sensor 242 or other sensor within the guiding catheter and at avariable distance from location of interest.

As mentioned above, the sensors such as sensors 240 and 242 and/or otheradditional sensors may include radiopaque markings. In some embodiments,the guidance catheter may also include radiopaque markings, such as in adistal portion including the distal end of the guidance catheter. Inthis way, the location of the sensor 240, 242 within the guidancecatheter can be seen by the clinician performing the procedure whilemeasuring P_(p).

FIG. 3 graphically illustrates several other possible sources of errorin measuring blood pressure, particularly as they may affect thecalculation of FFR, for example. FIG. 3 is a conceptual plot of bloodpressure, 340, as a function of time for a given patient, P(t). Onepotential error in calculating FFR is due to the fluctuations in bloodpressure due to the systolic and diastolic phases of the cardiac cycle342. Unless P_(d) and P_(p) are measured at substantially the same phaseof the cardiac cycle 342, there may be some amount of error introduced.Similarly, a more slowly varying source of error can also be introducedby the effect of the respiratory cycle (e.g., inspiration andexpiration) on blood pressure, as illustrated at 344 in FIG. 3. A thirdsource of error could be introduced by changes in the patient's posture,which could either raise or lower the overall pressure profile asindicated at 346 in FIG. 3. Embodiments of the invention which have theability to measure P_(d) and P_(p) substantially simultaneously, such asthe two-sensor embodiment shown in FIG. 2, may be able to minimize oreliminate the effects of such “timing errors” on the FFR calculation.Another method of addressing the effects of such “timing errors” will bediscussed below in the context of using a contrast injection system inconjunction with a sensor delivery device, according to some embodimentsof the invention.

In some embodiments, one or more of the sensors may be comprised of oneor more materials that together have a low thermal coefficient, such asa thermal coefficient of approximately zero. In some embodiments, thesensor is comprised of one or more materials that together have athermal coefficient of pressure of between approximately −0.1 and 0.1mmHg/° C. The portions of the sensor which contribute to the pressurereading may be comprised of a material having a low thermal coefficient.This may include, for example, any component which could change thewidth of the sensor cavity, which can change with pressure but alsocould change with temperature. This may be accomplished by constructingthe sensor from a set of materials with opposing thermal coefficients sothat the net thermal coefficient of the cavity is close to zero, such asbetween approximately −0.1 and 0.1 mmHg/° C. The use of one or moresensors having a low thermal coefficient may avoid errors which could becaused by the sensors moving out of calibration with atmosphericpressure as they are moved into the warmer environment of the patient'sbody, which could in turn result in erroneous calculations of FFR. Insome embodiments, one or more of the sensors may be comprised of amaterial having a thermal coefficient that is sufficiently low such thatthe sensor remains calibrated to atmospheric temperature after thetemperature of the sensor is changed from approximately room temperature(such as approximately 70-72 degrees F.) to approximately normal bodytemperature (such approximately 96-99 degrees F.) by insertion into theblood stream of a patient. The sensor or sensors comprised of a materialhaving a low thermal coefficient remain calibrated to atmosphericpressure after introduction into the bloodstream, while any sensors thatare comprised of a material having a higher thermal coefficient may bemoved out of calibration by the temperature of the blood stream. Becauseat least one of the sensors is comprised of a material having a lowthermal coefficient and remains calibrated to atmospheric pressuredespite being introduced into the body, any other device sensors whichare not comprised of a low thermal coefficient material can be correctedby equilibrating them to the sensor or sensors comprised of the materialhaving a low thermal coefficient.

Prior to use in a procedure, the sensor or sensors comprised of a lowthermal coefficient material may be calibrated to atmospheric pressureoutside of the patient's body. The sensors may then be interested intothe patient's blood stream as part of insertion of the device for theprocedure. If one of more of the sensors is not comprised of a lowthermal coefficient material, the sensors can then be equilibrated, withthe any sensor which is not comprised of a low thermal coefficientcalibrated to match a sensor having a low thermal coefficient. This maybe done after the sensors are positioned at a location proximal to thelocation of interest, before making pressure measurements. If allsensors are comprised of a material having a low thermal coefficient,the equilibration step may not be needed.

The benefit of using a sensor having a low thermal coefficient may beunderstood by considering the change in pressure due to temperaturedependent pressure sensing. This can be appreciated by the followingequation:

${FFR} = {\frac{P_{d}}{P_{A}} = \frac{P_{d} + P_{d}^{T} + \Delta}{P_{A} + P_{A}^{T}}}$

where P_(d) ^(T) is the pressure shift due to temperature of the distalsensor, P_(A) ^(T) is the pressure shift due to temperature of theproximal sensor, such as the aortic sensor, and Δ is the offsetintroduced when pressures are equalized. If the sensors are zeroedoutside of the body, at room temperature, and equalized while readingthe same pressure, then Δ=P_(A) ^(T)−P_(d) ^(T) and

${FFR} = {\frac{P_{d} + P_{A}^{T}}{P_{A} + P_{A}^{T}}.}$

The error in FFR due to the temperature dependence of the sensor istherefore:

$\frac{\delta \; {FFR}}{\delta \; P_{A}^{T}} = \frac{P_{A} - P_{d}}{\left( {P_{A} + P_{A}^{T}} \right)^{2}}$

The use of a sensor having a low thermal coefficient of pressure cantherefore be used in various embodiments to minimize the impact oftemperature changes upon the pressure measurement. The value of FFR atwhich the most accuracy is desired is at the treatment decision makingthreshold, which is typically an FFR of 0.8. In addition, the FFR ismeasurement may be obtained at a pressure of about 100 mmHG, which is atypical aortic pressure. In some embodiments, the sensor is designed tohave a thermal coefficient of pressure which results in an FFR error ofless than 0.01 due to the effect temperature at an FFR of 0.8 and apressure of 100 mmHg.

Referring again to FIG. 2, distal sleeve 220 may be substantiallytubular, as shown, or may have any shape that allows distal sleeve 220to slide over a medical guidewire 230 in an anatomical (e.g., vascular)structure of interest. In the context of measuring FFR in a coronaryartery, for example, it may be desirable that distal sleeve 220 besubstantially cylindrical in cross-section to minimize the totalcross-sectional area of the device. Distal sleeve 220 may be preferablyformed of a flexible material in some embodiments to facilitatepositioning and placement of the distal sleeve 220 (and sensor 240) overa guidewire 230 through narrow vascular structures such as coronaryarteries. In certain preferred embodiments, the distal sleeve 220comprises a flexible polyimide tube sized for placement in anatomical(e.g., vascular) structures of interest, such as in coronary arteries orperipheral arteries. In some embodiments, the distal sleeve 220 maycomprise a flexible microcoil tube. In some embodiments, flexibility maybe achieved and/or enhanced by applying a series of cuts along thesurface of the tube. For example, a plurality of cuts or notches along alength of the outer surface of distal sleeve 220 may be applied (e.g.,by laser cutting techniques known to those of ordinary skill in thisfield). Such cuts or notches may be substantially circumferentiallydirected, and may extend at least partially around the circumference ofthe distal sleeve. Successive cuts may be angularly offset from eachother to provide flexibility in all directions according to someembodiments.

The length of distal sleeve 220 may vary. In embodiments to be used incoronary arteries, for example, distal sleeve 220 may be up to about 15inches long, and in some preferred embodiments may be 11 inches long(e.g., to facilitate use deep within certain coronary arteries). In someembodiments, the distal sleeve 220 may also include a thin covering toprovide additional structural support and/or improve handlingcharacteristics of the device. Such a covering may comprise, forexample, polyester (PET) shrink tubing that substantially covers thedistal sleeve.

Distal sleeve 220 has a guidewire lumen 222 that is sized to slidablyreceive a guidewire 230 having an outer diameter between about 0.010inches and 0.050 inches. For making an FFR measurement in a coronaryartery 234, for example, the guidewire 230 may preferably have an outerdiameter of 0.014 inches, and guidewire lumen 222 would therefore needto have an inner diameter slightly larger than this to facilitateslidable movement of the distal sleeve 220 over the guidewire 230.

FIG. 4(a) shows an embodiment of the invention in which one or more flowholes 224 are disposed along a side portion of the distal sleeve 220(e.g., along the length of distal sleeve 220). Flow holes 224 couldallow blood to flow into the guidewire lumen 222 if an operator were topull back (e.g., withdraw) the guidewire 230 as shown in FIG. 4(a). Suchan embodiment may provide an improvement in accuracy in measuring thepressure drop across a stenosis, since the pressure drop attributable tothe device itself would be lessened by decreasing the effectivecross-sectional area of the device.

FIG. 4(b) is a cross-sectional view of an embodiment of the invention,illustrating the potential reduction in cross-sectional area that couldbe obtained by employing flow holes 224 in a side portion of distalsleeve 220. For example, by allowing blood to flow through flow holes224 into guidewire lumen 222, the effective cross-sectional area of thedevice 210 is reduced by the area of guidewire lumen 222, and any errorin blood pressure measurements caused by the flow obstruction of thedevice 210 itself would be accordingly reduced.

FIG. 5(a) is a cut-away side view of a portion of the device 210according to certain embodiments of the invention. FIG. 5(a) shows thedistal sleeve 220 and first sensor 240 of an embodiment in which sensor240 is provided with a certain degree of protection by being at leastpartially covered by a sensor housing 270 disposed on distal sleeve 220.Sensor housing 270 may be substantially tubular, or may besemi-circular, or may be any other shape that provides suitableprotection for sensor 240. Sensor housing 270 may be constructed oftubing such as polyimide, which is capable of being formed with arelatively thin wall thickness.

The sensor housing 270 may be constructed in several different ways, asdescribed with reference to FIGS. 5(a) through 5(e). Fiber opticsensors, for example, may be somewhat fragile, and should typically beprovided with some form of mechanical protection from stress and/orstrain relief. The sensing head of sensor 240 is generally attached tothe communication channel 260 (e.g., a fiber optic cable) with anadhesive. The sensing head can be prone to being pulled away from (e.g.,disconnected from) the fiber optic without much force because thebonding area is typically very small. FIGS. 5(a) through 5(e) illustrateseveral techniques that utilize a protective sensor housing 270surrounding the sensor 240 to minimize or eliminate the effects of suchstresses on the sensor 240.

One material which may be used to construct the sensor housing 270 is aheavy metal that is x-ray visible, such as platinum. A sensor housing270 formed of platinum may provide an x-ray marker band to facilitatethe placement and positioning of the sensor 240. A platinum sensorhousing 270 may be formed so it is generally thin, for example,approximately 0.001 inches in thickness. Such a thin-walled platinumsensor housing 270 may provide suitable protection to the sensor 240from stresses that might otherwise cause it to detach from thecommunication channel 260.

In some embodiments, sensor housing 270 may be shaped to facilitatemovement and placement of the device in the anatomical (e.g., vascular)structure of the patient. For example, as shown in FIG. 5(a), theforward and rearward portions 274 of sensor housing 270 may be formed atan angle (e.g., cut at an angle) to present a smoother, taperedstructure that is easier to navigate through anatomical (e.g., vascular)structures and passages in a patient (e.g., it allows the device 210 toslide through vascular passages such as arterial walls without catchingor snagging).

In some embodiments, sensor housing 270 may be formed as part of theprocess of forming distal sleeve 220. For example, a substantiallycylindrical mandrel may be used to form a distal sleeve 220 made of athermoset polymer (e.g., polyimide) by employing a dipping process. Aslight modification of this manufacturing process could employ a“housing forming element” located alongside the mandrel at the distalend of the mandrel. A single dipping process could thereby form sensorhousing 270 as an integral part of distal sleeve 220.

In some embodiments, an optional covering 226 may be applied over thesensor housing 270 and distal sleeve 220. Such a covering 226 mayfacilitate movement and positioning of the device 210 within ananatomical (e.g., vascular) structure of a patient. The covering 226 mayalso provide additional structural stability to the sensor 240, housing270, and distal sleeve 220 arrangement. An example of a class ofmaterials that may be suitable for forming covering 226 arethermoplastics. Such materials may sometimes be referred to asthin-walled heat-shrink tubing, and include materials such aspolyolefin, fluoropolymers (PTFE), polyvinyl chloride (PVC), andpolyester, specifically polyethylene terephthalate (PET). Forsimplicity, the term “PET tubing” will be used herein in reference toembodiments that incorporate such thin covering materials. The use ofPET tubing could be employed, for example, in embodiments with orwithout a housing 270.

PET tubing is a heat shrink tube made from polyester that exhibitsexcellent tensile strength characteristics, while having a wallthickness as little as 0.0002 inches. PET tubing may be used in someembodiments of the invention to encapsulate the distal sleeve 220. Thismay include, for example, encapsulating the sensor housing 270 and/or aportion of the communication channel 260 (e.g., the fiber optic cable),to the extent the communication channel 260 extends from the proximalportion 250. In some embodiments, the PET tubing may also extend tocover part of the proximal portion 250, for example, where it is coupledto the distal sleeve 220. In some embodiments, PET tubing may be used tohold a fiber optic communication channel 260 in place around the distalsleeve 220. After the PET tubing has been heat shrunk, one or moreopenings may be cut in the PET tubing, for example, to allow an exitport for the guidewire 230.

FIG. 5(a) shows a fluid opening 272 formed in one of the portions 274(e.g., the forward portion in this example) of the sensor housing 270.Fluid opening 272 allows fluid (e.g., blood) to enter the sensor housing270 and come into fluid contact with sensor 240. In embodiments thatincorporate a covering 226 (such as PET tubing), fluid opening 272 maybe formed in the covering 226.

FIG. 5(b) shows an embodiment of the invention where the fluid opening272 is formed in a side portion of the housing 270. This arrangement mayprovide a reduced likelihood of “clogging” within sensor housing 270,and/or a reduced likelihood of catching or snagging on any obstructionsor bends encountered while positioning device 210. For example, plaqueor calcium from arterial walls may enter the housing 270 as the deviceis moved through an artery; having the fluid opening 272 in a sideportion of housing 270 may reduce this effect. In some embodiments,allowing the PET tubing covering 226 to remain intact at the distal endof the housing 270 may prevent foreign material from entering thehousing 270 and possibly damaging the sensor 240, or affecting theaccuracy of pressure measurements. After the PET tubing covering 226 hasbeen heat shrunk over the device 210, holes can be punched through thecovering 226 as needed to form fluid openings 272 to allow fluid access(e.g., blood flow) inside the sensor housing 270.

In some embodiments of the invention, the inside portion of the sensorhousing 270 may be filled with a gel 278, such as a silicone dielectricgel. Silicone dielectric gels are often used with solid state sensors toprotect the sensor from the effects of exposure to a fluid medium, forexample. If the sensor housing 270 is filled with a gel 278 in front ofthe sensor diaphragm 279, then foreign material would be less likely topenetrate inside the housing 270. The gel 278 may also offer addedstructural stability to the sensor 240, and/or may enhance thepressure-sensing characteristics of the sensor 240. A gel 278 may beused in any of the embodiments of sensor housing 270 illustrated inFIGS. 5(a) to 5(d) and their equivalents.

In FIGS. 5(c) and 5(d), embodiments of the invention are shown whichinclude an optional marker band. If the sensor housing 270 is made frompolyimide tubing, for example, the device 210 may not show up as wellunder x-ray. An optional marker band 276 could be placed near the end ofthe distal sleeve 220. Marker band 276 may provide a visible indicationof the location of the sensor 240 when viewed under x-ray. As shown inFIG. 5(c), the marker band 276 on the end of the distal sleeve 220 mayprovide some structural reinforcement to the end of the distal sleeve220. In the alternative embodiment shown in FIG. 5(d), a marker band 276on the distal sleeve 220 located proximal of the sensor housing 270 mayreduce the likelihood of the marker band 276 becoming dislodged from thedevice 210. In some embodiments, it may be desirable to include a numberof such marker bands spaced at known distances (e.g., every 10 mm alongdistal sleeve 220, for example), such that the marker bands could beused to provide visual estimates of length or distance (e.g., to measurelesion length).

FIG. 5(e) shows an embodiment where a spacer 278 is used to providestrain relief at the connection between the sensor 240 and thecommunication channel 260. This strain relief may be made of anysuitable material, such as polyetheretherketone (PEEK), for example. Insome embodiments, spacer 278 may also be formed so as to serve as amarker band 276, substantially as described above. Spacer 278 could beemployed in embodiments with a sensor housing 270, or in embodimentswithout a sensor housing.

FIG. 6(a) shows an enlarged side view of a portion of the device 210according to one embodiment of the invention. The delivery tube(proximal portion 250) and distal sleeve 220 are preferably coupledtogether using a flexible bond method (medical adhesive) to maintainflexibility of the device 210. In some preferred embodiments, forexample, the proximal portion 250 will be bonded to an outer surface 221of the distal sleeve 220 in a bonding area 223. Bonding area 223 ispreferably disposed on distal sleeve 220 sufficiently proximal of thesensor 240 so that bonding area 223 is not within the vascular structureor passage of interest (e.g., it is not within the arterial vessel neara stenosis), but would still be inside the guiding catheter 232. Thejoining or bonding area 223 preferably maintains a degree of flexibilityin order to accommodate bends such as that in the aortic arch. Aspreviously noted, it may be desirable to minimize the width of thedevice 210 so that it can be passed through a relatively small guidingcatheter 232, for example. This goal may be achieved, at least in part,by causing the bonding area 223 to be as narrow as possible. In someembodiments, it is desirable to use the sensor delivery device 210inside a diagnostic guiding catheter 232, which are generally 4 Fr.

In some embodiments, the use of a distal transition 254 to couple theproximal portion 250 to the distal sleeve 220 may obtain a significantreduction in the width of the device 210. In certain preferredembodiments of the invention, the device 210 will be able to passthrough a 4 Fr guiding catheter 232. The embodiment of FIG. 6(a) has aproximal portion 250 that comprises a main section 252 and a distaltransition 254. Distal transition 254 extends distally from main section252 and is coupled to an outer surface 221 of distal sleeve 220 atbonding area 223. As shown in FIG. 6(a), the use of a distal transition254 to couple the proximal portion 250 to the distal sleeve 220 maycause a reduction in the width of the device 210 as compared to a device210 without the distal transition 254. This may be accomplished, forexample, in embodiments where the distal transition 254 is smaller incross-sectional area than main section 252. (Of course, the distaltransition 254 is optional and may not be required in all embodiments ofthe invention; the embodiments shown in FIGS. 1, 2, and 4, for example,do not include a distal transition. Such embodiments may result in asimpler manufacturing process, for example.)

In the embodiment shown in FIG. 6(a), distal transition 254 may besubstantially coaxial and/or concentric with main section 252, and issmaller in diameter than main section 252. In some embodiments, distaltransition 254 may be formed by inserting a hypotube inside the end ofthe proximal portion 250, the hypotube being of somewhat smallerdiameter than the proximal portion 250. The hypotube distal transition254 and the proximal portion may then be soldered together, as shown at256. The distal sleeve 220, which may comprise a thin walled tube formedof a material such as polyimide, may then be bonded to the smallerdiameter distal transition 254. Alternately, the distal sleeve 220 couldbe formed from a flat wire wound microcoil with PET tubing heat shrunkover the microcoil. An embodiment using a stainless steel microcoil forthe distal sleeve 220 might provide a lower coefficient of friction(than polyimide, for example) to reduce the sliding friction. However,such a microcoil embodiment would probably benefit from the use of a PETtubing covering 226 to provide reinforcement and/or a smooth surface.PET tubing may be used to form covering 226, as shown in FIG. 6(a), andsubstantially as described above. Once the PET tubing covering 226 hasbeen heat shrunk in the area of distal transition 254, for example,covering 226 may have one or more openings 227 formed in the PET tubing,for example, to create an exit port 227 for the guidewire 230, as shown.Note that, although only shown in FIG. 6(a), the embodiments shown inFIGS. 6(a), 6(b), and 6(c) may all include an optional covering 226(e.g., PET tubing), according to certain embodiments of the invention.

FIG. 6(b) shows an embodiment of the invention in which the longitudinalaxis of distal transition 254 is offset radially some distance “R” fromthe longitudinal axis of main section 252 to provide a further potentialreduction in the width of device 210, for example, to minimize thefootprint of device 210 and allow the use of a relatively small guidingcatheter. FIG. 6(c) shows an embodiment where the radial offset “R” isin an opposite direction from the offset “R” shown in FIG. 6(b). Thisarrangement may provide more clearance for guidewire 230 as it exitsdistal sleeve 220 in the area near distal transition 254.

FIGS. 6(a) and 6(b) also illustrate techniques that may be employed toform the distal transition 254. For example, the distal transition 254may be formed by welding or soldering a tubular member to the mainsection 252 as shown at 256. As shown, the tubular member 254 may extendinto the end of main section 252, and may include a communicationchannel 260 (e.g., an extension of communication channel 260 within mainsection 252). Alternately, the distal transition 254 may be formed by“swaging” a distal end of the main section 252, as shown at 256.“Swaging,” as that term is used herein, encompasses a number ofmanufacturing processes that reduce the diameter of a workpiece, forexample, by forcing the workpiece (or a portion thereof) through aconfining die, or by hammering a round workpiece into a smaller diameterworkpiece (e.g., rotary swaging or radial forging, for example).

Other methods of forming the distal transition 254 may include grinding(e.g., to reduce the outer diameter of a single piece from that of mainsection 252 to that of distal transition 254), or the use of adhesivesor glue (e.g., epoxy, ultraviolet adhesives, cyanoacrylates, etc.), orthermoforming, and/or other techniques known to those of ordinary skillin this area. FIGS. 6(d) and 6(e) show exemplary embodiments that may beformed by grinding or other comparable techniques, for example. Further,distal transition 254 need not extend into the main section 252 andcould instead be held in an abutting relationship to main section 252using certain of the aforementioned techniques.

FIGS. 6(a) and 6(b) happen to show embodiments of the invention in whicha distal transition 254 is employed to “setback” the main section 252from the distal sleeve 220 a distance “S” as shown. This may, forexample, be advantageous in creating additional “clearance” for theguidewire 230 as it exits the distal sleeve 220. However, the setback isnot a requirement, and embodiments of the invention may be employed witha zero setback, as shown in FIG. 6(c) (e.g., S=0).

FIG. 7(a) shows one possible embodiment of the invention in which asecond sensor 242 is coupled to a proximal sleeve 280, which therebyallows the first and second sensors 240, 242 to be spaced apart avariable distance, “V,” as shown. Proximal sleeve 280 in such anembodiment is adapted to be moved longitudinally (e.g., advanced and/orretracted) by an operator by sliding over proximal portion 250 toachieve the desired spacing, “V,” as shown.

FIG. 7(b) shows an alternate embodiment in which a multilumen shaft 290(e.g., formed of a polymer) includes a guidewire lumen 292, a sensorlumen 294 for an extendible/retractable first sensor 240 disposed on adistal end of an extendible/retractable sensor shaft 296, the sensorshaft 296 being slidably received within sensor lumen 294, and a secondsensor 242 coupled to an outer portion of the multilumen shaft 290. Thefirst and second sensors 240, 242 may be spaced a variable distanceapart (e.g., across a stenotic lesion of other anatomical location ofinterest in a patient) by slidably moving the sensor shaft 296 withrespect to the multilumen shaft 290 (e.g., by moving sensor shaft 296within sensor lumen 294).

FIG. 8 shows a device 210 according to an embodiment of the invention inwhich a proximal end of proximal portion 250 interconnects with a fiberoptic furcation tube 290 (e.g., in embodiments of the inventionemploying a fiber optic sensor). A fiber optic furcation tube 290provides an extension of the fiber optic communication channel 260 (fromthe sensor 240 through the proximal portion 250), to an optionalconnector 294, such as an “SC” fiber optic connector. (An SC connectoris a fiber optic connector with a push-pull latching mechanism whichprovides quick insertion and removal while also ensuring a positiveconnection. It also follows certain industry standards, allowinginterconnection with a variety of fiber optic devices which follow thesame standards.) Furcation tube 290 may, for example, be provided withSC connector 294 to allow the device 210 to send a signal from sensor240, for example, to other devices, monitors, fluid injection devices,display and control units, etc. Furcation tube 290 may comprise a Kevlarfiber reinforced tube (e.g., for strength) according to someembodiments. In some alternate embodiments, furcation tube 290 could beformed of coaxial tubing.

The length of furcation tube 290 may be chosen to extend from the device210 in the sterile field (e.g., where the patient is) to a locationoutside of the patient, such as a medical fluid injector, or to astandalone display device, or to some other processing or computingequipment 296 positioned some distance from the patient. The SCconnector 294 is adapted to interconnect with an injector (or othersignal processing unit) appropriately configured. If signal processingis done within the injector, then the injector display could be utilizedto display pressure waveforms and/or to calculate and display FFRvalues.

An alternate embodiment of the invention would be to construct a distalportion 300 of the sensor delivery device 210 using a dual lumenconfiguration. An example of such an embodiment is illustrated in FIG.9. One lumen of the distal portion 300 would accommodate the fiber opticcommunication channel 260 from the sensor 240 (and from sensor housing270, in some embodiments). The other lumen (e.g., guidewire lumen 222)would be adapted to slide over the guidewire 230 as shown. The guidewire230 in such an embodiment would exit from the dual lumen distal portion300 a certain distance (e.g., about 10-12 inches) back from (e.g.,proximal to) the sensor 240 through an opening 320 in the device 210. Insome embodiments, a stiffening wire 310 could be placed in the remainingproximal portion of the lumen 222 (that is, the portion of the guidewirelumen 222 in the proximal portion 250 of device 210). The stiffness ofthe stiffening wire 310 could be varied, for example, to aid a physicianin deploying and positioning the device 210 through a catheter and intoa particular anatomical (e.g., vascular) structure of interest. Thestiffening wire 310 could be part of the dual-lumen device 210, or couldbe an optional, removable item selected by a physician to obtain thedesired amount of stiffness according to some embodiments.

Another alternate embodiment of the invention would be an entirelyover-the-wire (OTW) device, substantially as shown in FIG. 10. FIG. 10illustrates an embodiment of the invention in which both the distalsleeve 220 and the proximal portion 250 of sensor delivery device 210are adapted to slide over a guidewire 230. The guidewire 230 in such anembodiment would not exit from or separate from the device 210 at somepoint along the length of device 210. Instead, the entire length of theproximal portion 250 of device 210 would slide over the guidewire 230within a guiding catheter (not shown). The design of the device mayincorporate two different sizes of tubes, for example, to form thedistal sleeve 220 and proximal portion 250. For example, a smallerdiameter thin-walled tube could form the distal sleeve 220, where thesensor 240 resides (optionally, within a sensor housing 270). Back somedistance from the location of sensor 240 on the distal sleeve 220, thesmaller diameter tube of the distal sleeve 220 would transition into alarger diameter portion (e.g., proximal portion 250), with sufficientclearance between the inner wall of both tubes and the guidewire. Suchclearance may provide less friction and sliding resistance whilepositioning the sensor 240, for example. The larger diameter tube of theproximal portion 250 could be made, for example, from a material with alow coefficient of friction to lower the sliding force. The sensor 240(and sensor housing 270, where applicable) could be of similarconstruction to that described above with respect to FIGS. 5(a)-5(d).

FIG. 10 is an example of an embodiment of the invention that illustratesthe over-the-wire concept. The larger diameter tubing of the proximalportion 250 could be formed of a single lumen tube or a dual lumen tube.With a single lumen tube, the communication channel 260 (e.g., fiberoptic) could be disposed on an outer surface of the proximal portion250, for example, and could extend toward a connector at a proximal endof the device 210. In embodiments with a dual lumen tube forming theproximal portion 250, the communication channel 260 could extend towarda connector at a proximal end of the device 210 within the second lumen.This could, for example, provide added protection for the communicationchannel 260 (e.g., fiber optic).

FIG. 11 is a flow diagram showing a method of using a sensor deliverydevice according to certain embodiments of the invention. In a preferredembodiment of the invention, for example, the method may be used toassess the severity of a stenotic lesion in a patient's vasculature.Step 1105 comprises placing a guidewire in a patient to a location ofinterest. In some embodiments, this may be a diagnostic guidewire, and aguiding catheter may also be inserted into the patient in conjunctionwith the guidewire. Step 1110 comprises deploying a sensor deliverydevice over the guidewire and out of the guiding catheter such that thesensor is positioned downstream of the location of interest (e.g.,downstream of a stenotic lesion). In some embodiments, the sensordelivery device will have a sensor mounted to a distal sleeve thatslides over the guidewire, and a proximal portion that is used toadvance the distal sleeve over the guidewire without having to move theguidewire. Step 1115 comprises using the sensor of the sensor deliverydevice to measure a physiological parameter of interest at the locationof interest. In some embodiments, the physiological parameter is bloodpressure downstream of a stenotic lesion, P_(d). Step 1120 comprisesmeasuring a reference value of the physiological parameter of interest.In some embodiments, this step comprises measuring blood pressureupstream of a stenotic lesion, P_(p). This could be done, for example,with a separate blood pressure monitoring apparatus, according to someembodiments, or could be done by repositioning the sensor deliverydevice to a location upstream of the stenotic lesion and making a secondpressure measurement with the sensor of the device. In some embodiments,the sensor may be positioned within the lumen of the guiding catheterfor measuring P_(p). Step 1125 may be an optional step which comprisescomparing the physiological parameter of interest measured at thelocation of interest to the reference value measured in step 1120. Insome embodiments, this may comprise calculating a ratio of the twomeasured values. In one preferred embodiment of the invention, step 1125comprises calculating FFR as the ratio of downstream to upstream bloodpressures, P_(d)/P_(p). Step 1130 may be an optional step whichcomprises providing an indication of the result obtained in step 1125.For example, step 1130 may comprise providing a visual indication of thecalculated FFR value, or may provide other visual cues (e.g., providinga color-coded indication of the severity of a stenotic lesion, such as ared indicator for FFR values less than 0.75, and a green indicator forFFR values equal to or greater than 0.75, as possible examples).

It may be desirable, as mentioned above with respect to FIG. 8, to havethe sensor delivery device 210 interact with other devices and/ordisplay equipment. For example, a furcation tube 290 and a connector 294may be used to send the signal (e.g., the measured physiologicalparameter signal) from sensor 240 to processing device 296. Processingdevice 296 could be, for example, a standalone display monitor to showsignal waveforms and/or numerical values of the physiological parametersignal from sensor 240. Processing device 296 could include datarecording capabilities in some embodiments. In certain preferredembodiments of the invention, processing device 296 could comprise amedical fluid injection system, such as a powered fluid injector used toinject contrast media and/or saline during certain imaging procedures(e.g., angiography, computed tomography, MRI, ultrasound, etc.). FIGS.12 and 13 illustrate exemplary powered injection systems which may beused with a sensor delivery device according to various embodiments ofthe invention.

FIG. 12 is a perspective view of one embodiment of a powered injectionsystem 1200 that may be used to perform various functions and, whenoperable, may be coupled to a physiological sensor delivery device, suchas the various embodiments of a sensor delivery device described above.The powered injection system 1200 shown in FIG. 12 may be used to injectmedical fluid, such as contrast media or saline, into a patient withinthe sterile field during a medical procedure (such as during anangiographic or CT procedure). A physiological sensor delivery devicemay be coupled to the system 1200 and used within the sterile fieldduring a patient procedure, according to one embodiment. The system 1200includes various components, such as a control panel 1202, ahand-controller connection 1204, a hand controller 1212, a fluidreservoir 1206, tubing 1208, a pump 1210, a pressure transducer 1218, afluid reservoir 1214, an injection syringe 1216, high pressure injectiontubing 1222, a valve 1220, an air detector 1224, and a stopcock 1226. Inone embodiment, described in more detail below, the fluid reservoir 1206comprises a container such as, for example, a bag or bottle of diluent(such as saline), the fluid reservoir 1214 comprises a container suchas, for example, a bag or bottle of contrast media, and the pump 1210comprises a peristaltic pump. In other embodiments, the pump 1210 maycomprise other forms of pumping devices, such as a syringe, a gear pump,or other form of displacement pump. In some embodiments, the injectionsyringe 1216 (along with its associated plunger), which is a pumpingdevice, may be replaced with another form of pumping device thatdelivers high-pressure fluid injections to a patient. An individualpumping device is capable of operating or functioning in different, ormultiple, operational modes. For example, a pumping device may beoperable to pump fluid when actuated, or driven, to move in a firstdirection (e.g., forward), while it may also be operable to move in asecond direction (e.g., an opposite direction, backward) to carry outcertain functions.

The system 1200 of FIG. 12 also shows a hand controller 1212 and an airdetector 1224. An operator may use the hand controller 1212 to manuallycontrol injection of saline and/or contrast media. The operator may pusha first button (not shown) on the hand control 1212 to inject saline,and may push a second button (not shown) to inject contrast, forexample. In one embodiment, the operator may push on the contrast buttonto deliver contrast at a variable flow rate. The harder the operatorpushes on the button, the greater the flow rate of contrast mediadelivered to the patient. Other controllers, such as foot pedalcontrollers, may also be used. The air detector 1224 is able to detectpotential air bubbles or columns within the high-pressure tubing 1222.In one embodiment, the air detector 1224 is an ultrasonic oracoustic-based detector. In other embodiments, the air detector 1224 mayuse infrared or other detection means (such as optical). If the airdetector 1224 detects the presence of air in the high-pressure tubing1222, it generates a signal that is used to warn the operator and/orhalt an injection procedure.

An operator may use the control panel 1202 to view and/or select variousparameters and/or protocols to be used during a given procedure. Thecontrol panel 1202 may be used to display information to an operatorabout the status of the equipment and/or the patient. The pump 1210 maybe used to pump saline from the bag into the patient via the salinetubing 1208, the valve 1220, and the high-pressure tubing 1222. In oneembodiment, the valve 1220 comprises a spring-based spool valve, as isknown in the art. In one embodiment, the valve 1220 comprises anelastomeric-based valve.

In one embodiment, the syringe 1216 is used to draw contrast from thereservoir 1214 into the syringe 1216, and to inject contrast from thesyringe 1216 into the patient via the valve 1220 and high-pressuretubing 1222. In one embodiment, the syringe 1216 is a self-purgingsyringe that has one port for filling of contrast and purging of air,and a second port for injection of contrast.

The valve 1220 may be used to control coupling between input ports tothe valve 1220 and an output port. In one embodiment, the valve includestwo input ports, one which is coupled to the contrast fluid line andanother which is coupled to the saline fluid line. The saline fluid linealso includes a pressure transducer 1218 for providing a signalrepresentative of patient blood pressure, for example.

The stopcock 1226 regulates the flow of fluids to the patient. In oneembodiment, the valve 1220 allows either the saline line or the contrastline to be coupled to the patient (high-pressure tubing) line 1222. Whenthe syringe 1216 is used to inject contrast media, for example, thevalve 1220 may allow the contrast media to flow to the patient line 1222while blocking the flow of saline to the patient line 1222. Valve 1220may operate such that the pressure transducer 1218 may also be blockedor isolated from the patient line 1222 during high-pressure injections,for example, to protect the transducer 1218 from high injectionpressures that may accompany a contrast injection. When there is noinjection of contrast from the syringe 1216, the valve 1220 may operateto block the contrast line from the patient line 1222, while opening thefluid connection between the saline line (tubing) 1208 and the patientline 1222. In this state, the pump 1210 is capable of injecting salineinto the patient, and the pressure transducer 1218 is also capable ofmonitoring hemodynamic signals coming from the patient via the patientline 1222 and generating representative signals based upon the measuredpressures.

As noted above, the system 1200 of FIG. 12 may be adapted to be coupledto a physiological sensor delivery device according to certainembodiments of the invention. System 1200 may, for example, be adaptedto receive the physiological signal generated by the sensor 240 ofdevice 210. In embodiments where the physiological signal from device210 is a pressure signal measured downstream of a stenotic lesion (e.g.,P_(d)), system 1200 may facilitate calculation of FFR, for example,since P_(p) may already be provided by pressure transducer 1218 ofsystem 1200. A visual or graphical display of the calculated FFR valuecould be presented to an operator via control panel 1202, for example.Since instantaneous values of P_(p) and P_(d) are available in such anarrangement, the timing effects and associated errors noted above withrespect to FIG. 3 would not pose a problem—simultaneous measurement ofP_(p) and P_(d) would reduce or eliminate such errors. In addition, timeaveraging or other signal processing could be employed by system 1200 toproduce mathematical variants of the FFR calculation (e.g., mean, max,min, etc.). Alternately, a time-varying display or plot of thecalculated FFR value could be displayed as a waveform (e.g., as afunction of time).

FIG. 13 is a perspective view of another embodiment of a poweredinjection system 1300 that may be used to perform various functions and,when operable, may be coupled to a physiological sensor delivery device,such as the embodiments described above. The powered injection system1300 shown in FIG. 13 may be used to inject medical fluid, such ascontrast media or saline, into a patient within the sterile field duringa medical procedure (such as during an angiographic or CT procedure). Aphysiological sensor delivery device may be coupled to the system 1300and used within the sterile field during a patient procedure, accordingto one embodiment.

The system 1300 of FIG. 13 is a dual-syringe system that includes acontrol panel 1302 and two motor/actuator assemblies 1303 a and 1303 b.Each motor drives one of the linear actuators in the assemblies 1303 a,1303 b. Each linear actuator drives a plunger of one syringe 1308 a or1308 b. An individual plunger moves within the syringe barrel of thesyringe 1308 a or 1308 b in either a forward or rearward direction. Whenmoving in a forward direction, the plunger injects liquid into thepatient line or purges air out of the syringe and into a liquidcontainer (e.g., bottle). When moving in a rearward direction, theplunger fills liquid into the syringe 1308 a, 1308 b from a liquidcontainer. FIG. 13 shows examples of two such liquid containers 1304 and1306. In one embodiment, the container 1304 is a bag or bottlecontaining contrast agent, and the container 1306 is a bag or bottlecontaining diluent, such as saline. In other embodiments, the syringes1308 a, 13808 b (along with associated plungers), which are each pumpingdevices, may either separately or together comprise another form ofpumping device that is capable of injecting fluids at appropriate flowrates/pressures/etc., such as, for example, a peristaltic pump oranother form of displacement pump. An individual pumping device iscapable of operating or functioning in different, or multiple,operational modes. For example, a pumping device may be operable to pumpfluid when actuated, or driven, to move in a first direction (e.g.,forward), while it may also be operable to move in a second direction(e.g., an opposite direction, backward) to carry out certain functions.Multiple sets of pinch valve/air detect assemblies are shown both FIG.13. One pinch valve/air detect assembly 1310 a is coupled between theliquid container 1306 and a syringe input port of the syringe 1308 a,and a second pinch valve/air detect assembly 1312 a is coupled between asyringe output port of the syringe 1308 a and the patient connection. Athird pinch valve/air detect assembly 1310 b is coupled between theliquid container 1304 and a syringe input port of the syringe 1308 b,and a fourth pinch valve/air detect assembly 1312 b is coupled between asyringe output port of the syringe 1308 b and the patient connection. Inthe embodiment shown in FIG. 13, each syringe 1308 a, 1308 b is adual-port syringe. Fluid flows and is drawn into the syringe 1308 a or1308 b from a container via the syringe input port, and fluid flows outof and is injected from the syringe 1308 a or 1308 b via the syringeoutput port.

Each pinch valve is a pinch valve/air detect assembly 1310 a, 1310 b,1312 a, 1312 b may be opened or closed by the system 1300 to control thefluid connections leading to or away from each of the syringes 1308 a,1308 b. The air detect sensors in the assemblies 1310 a, 1310 b, 1312 a,1312 b may be optical, acoustic, or other form of sensor. These sensorshelp detect air that may be present in the fluid connections leading toor away from the syringes 1308 a, 1308 b. When one or more of thesesensors generates a signal indicating that air may be present in a fluidline, the system 1300 may warn the user or terminate an injectionprocedure. The use of multiple pinch valves within the system 1300allows the system 1300 automatically, or through user interaction,selectively control the flow of fluid into or out of the syringes 1308a, 1308 b by opening or closing fluid tubing. In one embodiment, thesystem 1300 controls each of the pinch valves. The use of multipleair-detect sensors helps improve the overall safety of the system 1300by detecting possibly air (e.g., columns, bubbles) within fluid (in thetubing) leading to or away from the syringes 1308 a, 1308 b. Signalsfrom the air detectors are sent to and processed by the system 1300,such that the system 1300 may, for example, provide a warning, orterminate an injection procedure, if air is detected. In the example ofFIG. 13, the fluid tubing first flows through a pinch valve and thenflows through an air detector within the assemblies 1310 a, 1310 b, 1312a, 1312 b. In other embodiments, other configurations, ordering, and thelike may be used for the pinch valves and air detectors within theseassemblies. Moreover, other types of valves may be substituted for thepinch valves.

An operator may use the control panel 1302 to initialize, or setup, theinjection system 1300 for one or more injection procedures, and mayfurther use the control panel 1302 to configure one or more parameters(e.g., flow rate, volume of fluid to be delivered, pressure limit, risetime) of an individual injection procedure. The operator may also usethe panel 1302 to pause, resume, or end an injection procedure and begina new procedure. The control panel also displays variousinjection-related information to the operator, such as flow rate,volume, pressure, rise time, procedure type, fluid information, andpatient information. In one embodiment, the control panel 1302 may beconnected to a patient table, while being electrically coupled to themain injector of the system 1300. In this embodiment, the operator maymanually move the control panel 1302 to a desirable location, whilestill having access to all functionality provided by the panel 1302.

The system of FIG. 13 also includes a valve 1314 coupled to both outputlines coming from the syringes 1308 a and 1308 b. Each syringe outputprovides fluid injected through tubing that passes through a pinchvalve/air detect assembly 1312 a or 1312 b and that then leads to aninput of the valve 1314. In one embodiment, one fluid line to the valve1314 also includes a pressure transducer. The valve output port of thevalve 1314 is coupled to high-pressure tubing line, which is used todirect fluid to the patient. In one embodiment, the valve 1314 is madeof a flexible material, such as an elastomeric material. The valve 1314allows one of the fluid lines (e.g., the contrast line or the salineline) to be coupled to the patient (high-pressure tubing) line. Whensaline and contrast are contained within the syringes 1308 a and 1308 b,respectively, the valve 1314 allows the contrast media to flow from thesyringe 1308 b to the patient line (assuming the pinch valve in theassembly 1312 b is open and there has been no air detected), but blocksthe flow of saline from the syringe 1308 a to the patient line. Thepressure transducer coupled to the saline line (according to oneembodiment) is also blocked from the patient line, thereby protectingthe transducer from high injection pressures that may accompany acontrast injection. When there is no injection of contrast from thesyringe 1308 b, the valve 1314 blocks the contrast line from the patientline, but allows a connection between the saline line from the syringe1306 to the patient line. The syringe 1308 a is capable of injectingsaline into the patient (assuming the pinch valve in the assembly 1312 ais open and there has been no air detected), and the pressure transduceris also capable of monitoring hemodynamic signals coming from thepatient via the patient line, and generating representative electronicsignals based upon the measured pressures that can be processed by thesystem 1300.

In one embodiment, a secondary control panel (not shown) provides asubset of functions provided by the main panel 1302. This secondarycontrol panel (also referred to herein as the “small” control panel) maybe coupled to the injector within the system 1300. In one scenario, theoperator may use the small panel to manage injector setup. The smallpanel may display guided setup instructions that aid in this process.The small panel may also display certain error and troubleshootinginformation to assist the operator. For example, the small panel maywarn the operator of low contrast or saline fluid levels in the liquidreservoirs and/or syringes.

As with the system 1200 of FIG. 12, system 1300 of FIG. 13 may beadapted to be coupled to a physiological sensor delivery deviceaccording to certain embodiments of the invention. System 1300 may, forexample, be adapted to receive the physiological signal generated by thesensor 240 of device 210. Processing of the physiological signal fromsensor 240 (and/or from additional sensors of the sensor delivery device210, if applicable) may be performed within the injection system 1200 or1300, for example. Signal conditioning and/or processing may, forexample, be performed by a circuit board or card that may be an add-onfeature to system 1200 or 1300. Such a signal conditioning board or cardmay process a “raw” signal from sensor 240 and convert the signal into astandard analog and/or digital signal, which can be used by processorsof the injector system, according to some embodiments. The processedsignal may enable injector system 1200 or 1300 to display the signaldata (e.g., as pressure waveforms), and/or perform algorithms and/orcalculations and display the results.

In embodiments where the physiological signal from device 210 is apressure signal measured downstream of a stenotic lesion (e.g., P_(d)),system 1300 may facilitate calculation of FFR, for example, since P_(p)is already provided by the pressure transducer of system 1300. A visualor graphical display of the calculated FFR value, for example, could bepresented to an operator via control panel 1302, for example, or via asmall control panel (not shown) having a subset of the functionsprovided by control panel 1302. Since instantaneous values of P_(p) andP_(d) are available in such an arrangement, the timing effects notedabove with respect to FIG. 3 would not pose a problem. In addition, timeaveraging or other signal processing could be employed by system 1300 toproduce mathematical variants of the FFR calculation (e.g., mean, max,min, etc.).

FIG. 14 is a flow diagram of a method that may be performed according toone embodiment of the invention. The methods described herein may beperformed in varying degrees of automation, for example, by havinginstructions stored in a computer-readable medium and/or performed by acomputer or processor associated with a powered injection system (suchas the ones described above with respect to FIGS. 12 and 13, or othercomparable fluid injection systems). The method of FIG. 14 may, forexample, be used to assess the severity of a fluid flow restriction in apatient according to some embodiments of the invention. This method maybe performed using various powered injection systems, such as the system1200 shown in FIG. 12, or the system 1300 shown in FIG. 13. The orderingof the actions shown in FIG. 14 is for exemplary purposes only. In oneembodiment, a powered injection system may be capable of performing someof the steps of the method shown in FIG. 14 automatically, oralternately, after the operator has requested that the method becommenced through manual activation on the control panel (or secondarypanel, if available).

Step 1405 in FIG. 14 comprises placing a guidewire in a patient to alocation of interest, such as a stenotic lesion, or across a heartvalve, for example. In some embodiments, this may be a diagnosticguidewire, and a guiding catheter may also be inserted into the patientin conjunction with the guidewire. Step 1410 comprises deploying asensor delivery device over the guidewire such that the sensor ispositioned upstream of the location of interest (e.g., upstream of astenotic lesion, or on the high pressure side of a valve). In someembodiments, the sensor delivery device will have a sensor mounted to adistal sleeve that slides over the guidewire, and a proximal portionthat is used by an operator to advance the distal sleeve over theguidewire to the desired location without having to move the guidewire.Step 1415 comprises using the sensor of the sensor delivery device tomeasure a value of the physiological parameter upstream of the locationof interest. In some embodiments, the physiological parameter is bloodpressure, and the pressure measured by the sensor upstream of a stenoticlesion is the proximal pressure, P_(p).

Step 1420 in FIG. 14 comprises “normalizing” the P_(p) measurement madein step 1415 to the P_(p) measurement obtained from an independentsource. “Normalizing” the P_(p) measurement refers to the fact that anindependent source (e.g., a fluid sensor for monitoring patient bloodpressure during a procedure) will be used to obtain the P_(p) value thatwill be used for later comparisons or calculations with the P_(d) value(e.g., the downstream pressure) measured with the sensor of the sensordelivery device. The normalizing step basically ensures that the P_(p)value measured with the sensor equals the P_(p) value measured using theindependent source so that no error is introduced (or that any error isminimized) when a subsequent downstream pressure measurement (e.g.,P_(d)) is made. An adjustment, if needed, could be made to either P_(p)value, although it may often be simpler to adjust the sensor-based P_(p)value to match the independent source's P_(p) value.

Step 1425 comprises deploying the sensor delivery device over theguidewire such that the sensor is downstream of the location of interest(e.g., downstream of the stenotic lesion). Step 1430 comprises using thesensor of the sensor delivery device to measure a downstream value ofthe physiological parameter. In some embodiments, this step comprisesmeasuring blood pressure downstream of the stenotic lesion, P_(d). Step1435 comprises comparing the measured value downstream of the locationof interest (e.g., P_(d), downstream blood pressure) to a value measuredupstream of the location of interest using the independent source (e.g.,P_(p)). In some embodiments, the comparison made in step 1435 maycomprise calculating a ratio of the two measured values. In onepreferred embodiment of the invention, step 1435 comprises calculatingFFR as the ratio of downstream to upstream blood pressures, P_(d)/P_(p).Step 1440, which may be an optional step, comprises providing anindication of the result of the comparison made in step 1435. Forexample, step 1440 may comprise providing an indication of thecalculated FFR value (e.g., numerical or graphical display or plot),and/or other cues may be provided to an operator. A color-codedindication of the severity of a stenotic lesion may be provided, forexample, a RED indicator for FFR values less than 0.75, and/or a GREENindicator for FFR values equal to or greater than 0.75. Other examplesof indicators are possible, including non-visual indicators—an audibleindication, an alarm sound for example, could alert an operator of anFFR value that is less than 0.75, which may prompt the operator to makea therapy decision.

FIG. 15 is a flow diagram of a method that may be performed according toan embodiment of the invention. The method of FIG. 15 may, for example,be used to assess the severity of a fluid flow restriction in a patientaccording to some embodiments of the invention. The method of FIG. 15employs a sensor delivery device 210 having a first and second sensor240, 242, such as the devices 210 shown in FIGS. 2 and 7. This methodmay also be performed in conjunction with various powered injectionsystems, such as the system 1200 shown in FIG. 12, or the system 1300shown in FIG. 13. The ordering of the actions shown in FIG. 15 is forexemplary purposes only.

Step 1505 in FIG. 15 comprises placing a guidewire in a patient to alocation of interest, such as a stenotic lesion, or across a heartvalve, for example. In some embodiments, the guidewire may be adiagnostic guidewire, and a guiding catheter may also be inserted intothe patient in conjunction with the guidewire. Step 1510 comprisesdeploying a sensor delivery device over the guidewire such that a firstsensor of the sensor delivery device is positioned upstream of thelocation of interest, and a second sensor of the sensor delivery deviceis positioned downstream of the location of interest. The second sensormay be positioned such that it is located within the guiding catheter.In an embodiment such as that described above with respect to FIG. 7, anoptional step may next be performed wherein a proximal sleeve 280 ismoved by an operator relative to the rest of device 210 in order to varythe distance, V, between first sensor 240 and second sensor 242 whilepositioning the second sensor 242 within the guiding catheter. In anembodiment such as that described above with respect to FIG. 2, itshould be noted that more than two sensors could be mounted along device210, and that the spacing between adjacent sensors could vary as well,according to some embodiments of the invention. Step 1515 comprisesusing the first sensor to measure an upstream value of the physiologicalparameter, and using the second sensor to measure a downstream value ofthe physiological parameter, such as from within the guiding catheter.

Step 1535 comprises comparing the measured value downstream of thelocation of interest (e.g., P_(d), downstream blood pressure) to thevalue measured upstream of the location of interest (e.g., P_(p)). Insome embodiments, the comparison made in step 1535 may comprisecalculating a ratio of the two measured values. In one preferredembodiment of the invention, step 1535 comprises calculating FFR as theratio of downstream to upstream blood pressures, P_(d)/P_(p). Step 1540,which may be an optional step, comprises providing an indication of theresult of the comparison made in step 1535. For example, step 1540 maycomprise providing an indication of the calculated FFR value (e.g.,numerical or graphical display or plot), and/or other cues may beprovided to an operator. A color-coded indication of the severity of astenotic lesion may be provided, for example, a RED indicator for FFRvalues less than 0.75, and/or a GREEN indicator for FFR values equal toor greater than 0.75. Other examples of indicators are possible,including non-visual indicators—an audible indication, an alarm soundfor example, could alert an operator of an FFR value that is less than0.75, which may prompt the operator to make a therapy decision.

Although not shown in FIGS. 11, 14, and 15, any of these methods couldbe performed with an embodiment of device 210 having flow holes 224,such as the device of FIGS. 4(a) and 4(b). Using such a device, themethods may optionally include a step wherein an operator retracts theguidewire 230 to allow fluid flow (e.g., blood flow) through flow holes224 into the guidewire lumen 222 of the distal sleeve 220. Performingthis optional step prior to measuring downstream pressure, P_(d), mayreduce the amount of flow restriction caused by the device 210 itself,and may thereby reduce the measurement error.

In some embodiments, a method may include basing a therapy decision onthe calculated FFR value, e.g., if the calculated FFR is less than 0.75,an interventional therapy is recommended and/or performed. In someembodiments, an interventional therapy device may be deployed bywithdrawing sensor delivery device 210, and using the same guidewire 230to deploy the interventional therapy device.

FIG. 16 is a perspective view of a powered injection system adapted tobe coupled to a physiological sensor delivery device according tocertain embodiments of the invention. FIG. 16 shows a sensor deliverydevice 210 connected to a powered injection system 1630 via furcationtube 290 and connector 294. Injection system 1630 is adapted to receivea physiological measurement signal (e.g., blood pressure) from device210 via input port 1650. In preferred embodiments, the signal is anoptical signal, and connector 294 is an SC fiber optic connector adaptedto mate with port 1650 to receive the optical signal.

As shown in FIG. 16, system 1630 has 2 fluid containers 1632, 1634,which are adapted to deliver fluid through lines 1633 and 1635. Fluid inline 1633 (e.g., contrast solution) may be delivered at significantlyhigher pressures than fluid in line 1635 (e.g., saline solution), forexample. Valve 1620 may be used to control coupling between input portsto the valve 1620 and to an output port which ultimately leads to apatient via patient line 1622. In one embodiment, valve 1620 includestwo input ports, one which is coupled to a contrast fluid line 1633 andanother which is coupled to a saline fluid line 1635. The saline fluidline is also coupled to a pressure transducer 1618 for providing asignal representative of patient blood pressure, for example. The signalfrom pressure transducer 1618 may be communicated to system 1630 viacommunication path 1640 and connector 1642, or via other equivalentmeans (e.g., infrared, optical, etc.).

In one embodiment, the valve 1620 allows either the saline line or thecontrast line to be coupled to the patient (high-pressure tubing) line1622. When the system 1630 is injecting contrast media, for example, thevalve 1620 may allow the contrast media to flow to the patient line 1622while blocking the flow of saline to the patient line 1622. Valve 1620may operate such that the pressure transducer 1618 may also be blockedor isolated from the patient line 1622 during high-pressure injections,for example, to protect the transducer 1618 from high injectionpressures that may accompany a contrast injection. When there is noinjection of contrast from the system 1630, the valve 1620 may operateto block the contrast line from the patient line 1622, while opening thefluid connection between the saline line (tubing) 1635 and the patientline 1622. In this state, the system 1630 may be capable of injectingsaline into the patient, while the pressure transducer 1618 is capableof monitoring hemodynamic signals coming from the patient via thepatient line 1622, and generating representative signals based upon themeasured pressures.

FIG. 16 shows control panel 1602 connected to injection system 1630 viacommunication path 1660. An operator may interact with system 1630 viacontrol panel 1602 (or via a secondary panel, if available) to reviewand/or modify injection parameters, for example. In a preferredembodiment of the invention, system 1630 is adapted to receive pressuresignals simultaneously from pressure transducer 1618 and from device210, representative of downstream and upstream pressures (e.g., P_(d),P_(p)), respectively. Thus, in a preferred embodiment, system 1630receives P_(d) and P_(p) signals substantially simultaneously, comparesthe two signals (e.g., calculates FFR=P_(d)/P_(p)), and provides anindication of the result of the comparison to an operator via a displayscreen 1670 of control panel 1602. As noted above, the indication of theresult of the comparison may take a number of different forms, includingnumerical, graphical, time plots, etc. The indication may be of thepass/fail variety, for example, indicating one color-coded pattern(e.g., a RED icon) for an FFR value below a certain value (e.g., 0.75),and/or a different color-coded pattern (e.g., a GREEN icon) for an FFRvalue at or above a certain value (e.g., 0.75). The indication may alsobe an audible alarm according to some embodiments of the invention.

FIG. 17 is an idealized view of information that may be displayed (e.g.,via an interactive graphical user interface, or “GUI interface”) to anoperator, according to certain embodiments of the invention. FIG. 17shows a GUI screen that may be displayed either via a control panel thatis unique to the sensor delivery device 210, or via a control panel of adevice adapted for use with device 210, such as the powered fluidinjection systems described above with respect to FIGS. 12, 13, and 16.(The GUI interface could be implemented in software such that a usermight see a very similar screen regardless of whether a stand-alonedisplay device or an integrated injector system was being used,according to various embodiments of the invention.)

In FIG. 17, screen 1702 is adapted to display data in various forms(e.g., waveform data, numerical data, calculated values, patientinformation, device status information, etc.). For example, in apreferred embodiment of the invention useful for making FFRmeasurements, blood pressure waveforms may be displayed as a function oftime for both proximal pressure, P_(p)(t) 1704, and distal pressure,P_(d)(t) 1706. In some embodiments, systolic and diastolic bloodpressure measurements may be superimposed on the time plot for theproximal (e.g., aortic) pressure waveform, as shown at 1708 and 1710,respectively, and/or may be calculated as average values and displayedsubstantially as shown at 1712. Similarly, average values for proximalpressure 1704 and distal pressure 1706 may be calculated (e.g., thesecould be time-weighted averages, moving averages, etc.) and displayed asshown at 1714 and 1716, respectively. A calculation of FFR based onproximal pressure 1704 and distal pressure 1706 may also be calculatedand displayed as shown at 1718, for example (e.g., FFR equalsP_(p)/P_(d), and the values used for P_(p) and P_(d) could be averagesor other forms of statistical or numerical representation), according tosome embodiments of the invention. Further, some embodiments may includea feature to alert an operator to an FFR value that lies outside of anormal range (e.g., less than 0.75) to indicate, for example, that someother action should be taken (e.g., select and perform an interventionaltherapy). This could be a visual cue (such as a colored light, as shownat 1720), or could be an audible cue (such as an alarm sound, forexample).

The screen 1702 of FIG. 17 shows various additional features which maybe (optionally or alternately) incorporated in various embodiments.Status area 1722, for example, may provide information about thepatient, date/time, the site within a particular patient, the status ofthe sensor, and an indication of whether the sensor signal has been“normalized” to another pressure monitoring signal. A normalizationbutton 1724 may be included in some embodiments, and could be used, forexample, to normalize the pressure signal from a sensor of sensordelivery device 210. Normalization might be done during a procedure inwhich an FFR measurement is desired (e.g., to assess the severity of astenosis). When a sensor of sensor delivery device 210 is positionedupstream of the stenosis, the measured pressure using the sensor shouldbe equal to the proximal pressure measured using normal blood pressuremonitoring equipment (e.g., via the pressure transducer 1618 of theinjection system shown in FIG. 16, for example). In one embodiment, anoperator would position the sensor 240 of sensor delivery device 210upstream of a location of interest and press the normalization button1724 of screen 1702, which could then automatically adjust or calibratethe pressure signal from sensor 240 to match the proximal pressuremeasured using normal blood pressure monitoring equipment.

The screen 1702 of FIG. 17 may also include navigational features, insome embodiments, which may allow an operator to view and recordinformation that may be of interest. For example, a cursor button 1726may allow an operator to position a marker or cursor 1727 to a point ofinterest on the waveforms 1704, 1706, which could provide instantaneousmeasured values of P_(p)(t) 1704 and P_(d)(t) 1706 at a selected pointin time. In some embodiments, an operator may elect to save the cursoreddata by pressing a “save” button 1728, which could save the highlighteddata for review at a later point in time. A review button 1730 may beprovided for this purpose in some embodiments, allowing a user tocompare previous historical measurements to current ones and use thisinformation to make diagnostic and therapeutic decisions. In someembodiments, it may be desirable to include a “zoom” feature, forexample, to analyze the data. For example, an operator may wish to zoomin (e.g., via the +arrow of zoom 1732) to look more closely at certaindata, or may instead wish to zoom out (e.g., via the −arrow of zoom1732) to evaluate overall trends, for example.

A Physiological Sensor Delivery Device has been described in connectionwith exemplary embodiments and exemplary preferred embodiments andimplementations, as examples only. It will be understood by those havingordinary skill in the pertinent art that modifications to any of theembodiments or preferred embodiments may be easily made withoutmaterially departing from the scope of the appended claims.

What is claimed is:
 1. A sensor delivery device comprising: a distalsleeve configured to be advanced through a patient's vasculature over aguidewire; a proximal portion; and a pressure sensor located on thedistal sleeve or the proximal portion and adapted to generate a signalproportional to fluid pressure, wherein the pressure sensor comprises amaterial having a low thermal coefficient of pressure.
 2. The sensordelivery device of claim 1, wherein the thermal coefficient of pressureof the material ranges from approximately −0.1 to 0.1 mmHg/° C.
 3. Thesensor delivery device of claim 2, wherein, when the sensor iscalibrated to atmospheric pressure outside of a patient's body atapproximately room temperature, the material having the low thermalcoefficient of pressure is configured to keep the sensor calibrated toatmospheric pressure after the sensor is inserted into a patient's bodyand during advancement of the sensor to a region of interest within thepatient's body.
 4. The sensor delivery device of claim 1, wherein thoseportions of the sensor contributing to generation of the signalproportional to fluid pressure include the material having the lowthermal coefficient of pressure.
 5. The sensor delivery device of claim1, wherein the pressure sensor includes a portion that defines a sensorcavity, wherein a size of the sensor cavity is variable, and wherein theportion that defines the sensor cavity includes the material having thelow thermal coefficient of pressure.
 6. The sensor delivery device ofclaim 5, wherein the pressure sensor is a fiber optic pressure sensor.7. The sensor delivery device of claim 5, wherein the portion thatdefines the sensor cavity further includes another material having ahigh thermal coefficient of pressure that is generally opposite the lowthermal coefficient of pressure such that a net thermal coefficient ofpressure of the portion that defines the sensor cavity ranges fromapproximately −0.1 to 0.1 mmHg/° C.
 8. The sensor delivery device ofclaim 1, further comprising: a second pressure sensor located on thedistal sleeve or the proximal portion and proximal to the pressuresensor, and wherein the second pressure sensor is adapted to generate asignal proportional to fluid pressure.
 9. The sensor delivery device ofclaim 8, wherein the second pressure sensor comprises the materialhaving the low thermal coefficient of pressure.
 10. The sensor deliverydevice of claim 8, wherein the second pressure sensor is located on theproximal portion.
 11. A method of measuring Fractional Flow Reserve(FFR) in a patient, the method comprising the steps of: calibrating afirst pressure sensor of a sensor delivery device to atmosphericpressure while located outside of the patient, wherein the firstpressure sensor comprising a first material having a low thermalcoefficient of pressure; after calibrating the first pressure sensor,advancing the sensor delivery device to a location of interest withinthe patient's body; measuring a reference pressure proximal to thelocation of interest; measuring a distal pressure distal to the locationof interest using the first pressure sensor; and calculating FFR usingthe measured distal pressure and the reference pressure.
 12. The methodof claim 11, wherein the thermal coefficient of pressure of the firstmaterial ranges from approximately −0.1 to 0.1 mmHg/° C.
 13. The methodof claim 12, wherein the first sensor is calibrated to atmosphericpressure outside of a patient's body at approximately room temperature,and wherein after calibrating the first sensor the first material havingthe low thermal coefficient keeps the first sensor calibrated toatmospheric pressure while the first sensor is advanced to the locationof interest within the patient's body.
 14. The method of claim 11,wherein the first pressure sensor includes a portion that defines asensor cavity, wherein a size of the sensor cavity is variable, andwherein the portion that defines the sensor cavity includes the firstmaterial having the low thermal coefficient of pressure.
 15. The methodof claim 14, wherein the portion that defines the sensor cavity furtherincludes a second material having a high thermal coefficient of pressurethat is generally opposite the low thermal coefficient of pressure suchthat a net thermal coefficient of pressure of the portion that definesthe sensor cavity ranges from approximately −0.1 to 0.1 mmHg/° C. 16.The method of claim 11, wherein the sensor delivery device furthercomprises a second pressure sensor comprising a second material having anon-low thermal coefficient of pressure.
 17. The method of claim 16,further comprising the steps of: equilibrating the second pressuresensor to the first pressure sensor while the first pressure sensor andthe second pressure sensor are within the patient's body; afterequilibrating the second pressure sensor, positioning the first pressuresensor distal to the location of interest and measuring the distalpressure using the first pressure sensor; and after equilibrating thesecond pressure sensor, positioning the second pressure sensor proximalto the location of interest and measuring the reference fluid pressureusing the second pressure sensor.
 18. The method of claim 17, whereinFFR is calculated after equilibrating the second pressure sensor to thefirst pressure sensor.
 19. The method of claim 16, wherein the secondmaterial has the non-low thermal coefficient of pressure outside of arange from approximately −0.1 to 0.1 mmHg/° C.
 20. The method of claim11, further comprising the step of: withdrawing the sensor deliverydevice and deploying an interventional therapy device using a sameguidewire used to position the first sensor distal to the location ofinterest.